CN103619406A

CN103619406A - Method and system for combining anatomical connectivity patterns and navigated brain stimulation

Info

Publication number: CN103619406A
Application number: CN201280027220.2A
Authority: CN
Inventors: 屠奥马斯·内乌沃宁; 亨利·汉努拉
Original assignee: Nexstim Oyj
Current assignee: Nackers Tim Public Co. Ltd.
Priority date: 2011-06-03
Filing date: 2012-06-04
Publication date: 2014-03-05
Anticipated expiration: 2032-06-04
Also published as: US11951324B2; EP2714192A1; US20210283412A1; RU2013158141A; JP2017202344A; JP6650913B2; PL2714192T3; JP6242787B2; US20130178693A1; CN103619406B; WO2012164172A1; EP2714192B1; US20170326377A1; JP2014515296A; ES2869957T3

Abstract

When operating a brain stimulation device, it is critical to understand and control the network effects associated with the area being targeted for stimulation. A combined system and a method which are provided by the invention provide the operator with a real-time view of the brain network potentially affected by the stimulation. The system and the method are capable of increasing the accuracy of diagnostic information. Additionally, disclosed herein are a system and a method for combining navigated brain stimulation data and anatomical data with brain connectivity data for an individual.

Description

For combining the method and system of dissecting connection mode and navigation brain stimulation

Technical field

The present invention relates to the mapping of brain function and treat disease by brain stimulation system, the dissection in especially definite brain and the relation in function.

Background technology

The object that operates brain stimulation device on patient's brain can be for diagnostic purpose, to cause the response of bringing out property, or for therapeutic purposes, causes the provisional or permanent variation of brain function.The effectiveness of brain stimulation method depends on how stimulating apparatus and stimulation energy arrive the expectation anatomic region of institute's targeting well.

A solution is to realize stimulating apparatus with respect to the location of the targeting anatomic part of health with 3 D positioning equipment.Conventionally, stereotaxis guider is used anatomic image (from the structural images of MRI or CT) so that stereotactic apparatus is associated with individual dissection structure.Yet the brain anatomical structure of accepting the main body of stimulation is changed or has destroyed repeatedly by wound or tumor.Therefore, the anatomic image of main body brain may be not enough to determine specific part functional of brain.

Diagnosis or treatment stimulate can have local or long-range effect, and this depends on the anatomy of target area and the relation in function.Therefore, need a kind of operator that be used to stimulating apparatus that the method and system of the accurate view of the specific basic anatomical structure of individual brain, connection and function is provided.

Summary of the invention

An aspect of some embodiments of the present invention is that a kind of more complete and real view of brain network of the potential impact being upset is provided for the operator of navigation brain stimulation system.

Another aspect of some embodiment is to provide a kind of system and method that can improve the accuracy of diagnostic message.

In addition, another aspect of some embodiment is that navigation brain stimulation is combined with the brain connection data from individual.

According to some embodiment of the present invention, the method for combination of stimulation navigation and performance data has been described herein.These methods can be by intrusive mood brain stimulations or preferably by non-intrusion type, through cranium, are stimulated to implement.This method comprises some or all of following steps: obtains one or more anatomic images of brain, obtains the performance data of brain, and combination anatomic image and performance data.The example of anatomic image has MRI image and CT image.The example of performance data has positron emission computerized tomography (PET) data, functional mri (fMRI) data and diffusion tensor imaging (DTI) data.

In addition, according to the system of some embodiment of the present invention, comprise the 3 D positioning equipment that can be used for guiding with respect to brain anatomical structure stimulating apparatus.Useful guider is directed to a suitable anatomical position by described stimulating apparatus, and this stimulating apparatus is actuated herein, and introduces electric field in a part for brain or in a part for brain.

According to some embodiment, can reduce the uncertainty relevant to existing brain mapping method, the uncertainty that the image especially providing by proper technology guiding (navigation) transcranial magnetic stimulation and white matter fiber are followed the tracks of.In addition, also can help the layout of cortex or deep brain stimulation device in as the planning of operation at therapeutic intervention.In addition, the information that embodiments of the invention come from the different current imaging modes using by integration makes excision safer.In addition the quantitative information that, different diagnostic modes are provided by providing embodiments of the invention helps to make the decision-making of operation more objective.

Embodiments of the invention have been described to be connected to and have been comprised real-time physical modeling and the stimulating apparatus that is connected the navigation system of tracking system.Combined system provides the real-time view of the brain network of the impact that may be upset for operator.In addition, not only can carry out modeling to stimulating unit, and can carry out modeling and demonstration to the prediction effect of stimulating unit.

According to some embodiment aspect, advantageously for stereotactic system, provide the demonstration (as positron emission computerized tomography (PET) or Functional MRI (fMRI)) of performance data, so that the highlighted demonstration functional activity region relevant to operation.In addition the progress that, is called the MRI technology of diffusion tensor imaging (DTI) has made by the formed part of alba, to be connected with long-range dissection by mapping.By dissecting link information and be added on the localization part of cerebral irritation device, to enrich the getable information of operator, caused the better understanding to diagnostic message, and the wiser targeting to for example therapeutic stimulation.

When operation brain stimulation device, importantly should understand and control the network effects that are associated with the region that is just stimulated institute's targeting.This combined system provides the real-time view of the brain network of the impact about being upset for operator.

Accompanying drawing explanation

Fig. 1 has shown the position (left side) of the stimulation field recording in the mapping session illustrating in NBS system.The position of the intracortical maximum field of NBS computed in software, and according to its corresponding peak-peak MEP amplitude, it is carried out to color coding, thus make thermal map.In thermal map, by white, to drawing the position of maximum MEP, carry out color coding (enlarged drawing, the right side).

Fig. 2 has shown the DICOM output of the focus stimulation sites illustrating on NBS screen.The MEP peak response that is abductor pollicis brevis (APB) for maximum hand muscle is defined as " focus ", and it is as the seed zone of the fibre bundle imaging tracking (tractography) of tractus pyramidalis.APB focus is in close proximity to tumor.

Fig. 3 has shown the combination of patient's MRI data set, NBS map image and DT imaging data.After image co-registration, from the MEP map of NBS Motion mapping session, will be presented in three-dimensional navigation image, and can be as seed region with application fibre bundle imaging tracking algorithm, thereby demonstrate the white matter bundle of primary motor cortex.Position color coding for the maximum MEP response of the APB muscle for seed region be green.

Fig. 4 has shown and the result of fibre bundle imaging tracking is not being done to any post processing is converted to the image of 3D object with the fiber of the APB focus that is derived from Fig. 2 after in outputing to navigation system.Tumor marker is red, and APB focus is shown as yellow spheroid.

Fig. 5 shows for combining DTI and NBS(or other to be stimulated) example of the parts of the system of data.

Fig. 6 shows for combining other example of parts of the system of DTI and NBS data.

Fig. 7 shows an example of the concept being connected between seed position and IC dark distant object.

Fig. 8 has shown an example of the concept that connects two Interhemispheric callus white matter fibers.

The specific embodiment

Can use the computer assisted stereotaxis navigation system being associated with stimulating apparatus to determine the central nervous system's who stimulates institute's targeting part, so that diagnostic message or effect that the layout of guiding stimulation probe or explanation are caused by stimulating apparatus.

Intrusive mood and non-intrusion type stimulating apparatus have different technical limitations.Intrusive mood stimulating apparatus can be placed to the tissue being stimulated and directly contact.Intrusive mood device is considered to directly to activate the tissue directly contacting with stimulation probe.

Non-intrusion type stimulating apparatus must depend on the rough estimate of effect of stimulation conventionally, or depends on the modeling of the real-time or off-line of effect of stimulation.Intrusive mood technology can be used modeling and the estimation of the real-time or off-line of effect of stimulation, in particular for the installation of planning implant and the adjustment of the stimulus parameter after installation and/or experimental period.

Below several non-limiting examples of real-time and/or off-line modeling.For example, can determine that mobilizing function (AF) is to estimate deep brain stimulation (DBS) probe activation volume around.Mobilizing function has been described the electric field of being introduced by stimulation probe, wherein causes volume and the shape of the electric field of this activation to depend on many device parameters.The effect that depends on the viewed or prediction that the activation by stimulating apparatus causes, operator can wish to change stimulus parameter to mate desirable stimulus field pattern, the basic anatomical structure that it can mate better.

Another example is from the field of transcranial magnetic stimulation (TMS).Can adopt computer assisted stereotactic system that coil is placed on suitable anatomic region.Then can to the effect of TMS coil, carry out modeling by physical modeling system or program, be presented at brain surface upper or at the coil enable mode of IC one or more depths.Conventionally, TMS coil activates pattern and has stimulation focus, has the region of the electric field intensity higher than peripheral region.The size in this region that experience superthreshold stimulates changes according to the output of stimulator.This region has activation area (AA) or activation volume (AV).

Here provided an example that connects tracking system.Can use the technology that is called diffusion tensor imaging (DTI) to study the dissection connection between brain district.The water diffusion imaging of DTI based on using nuclear magnetic resonance.Use a plurality of mathematics post processings to the image of water diffusion-sensitive and image, can in one or more visual volume elements (as voxel), show the preferred orientations of water diffusion.

Show, through the alba aixs cylinder of voxel, aim at the preferred orientations of diffusion.In addition, can build the visual of virtual aixs cylinder bundle or fiber by one or more mathematical methods.This technology is called as (white matter) fiber tracking in the literature.

First typical fiber tracking algorithm has utilized diffusion-sensitive MR data as fibre bundle imaging tracking algorithm, and some boundary conditions that define algorithm are as the parameter of startup and stopping criterion, step-length, the upper limit of fibre length, possible curvature of fiber limit value etc.Its objective is and help this algorithm to find significant fiber on physiology.Possible parameter and the list of value thereof are well-known to those having ordinary skill in the art.

Fiber tracking algorithm can generate the fiber of any amount from given data, but often only needs the visual of fibre bundle that anatomy is relevant.Conventionally, operator set follow the tracks of or visualization system starting point (A) and halt (B).As a result, only have those to connect A to B(or contrary) and the fiber that meets boundary condition be shown.It is simple or loaded down with trivial details setting target area.Anatomical knowledge under cortex based on known, can identify some main structures, and for example posterior limb of internal capsule (PLIC) or pons decline by them from the fiber of motor cortex.But, set cortex target area more much more difficult and non-apparent.In addition,, when under cortex or cortex, pathological changes exists, setting significant target area (A or B) may be very difficult.

Embodiments of the invention have been described to be connected to and have been comprised physical modeling system (in real time or off-line) and the stimulating apparatus being connected in the navigation system of tracking system.The effect of some embodiment is, can be for limiting target area (A or B) for the volume of the mobilizing function (AF) described in the document of DBS.Similarly, for TMS or other non-intrusion type stimulating method, activation volume or activation area can be used for objective definition region (A or B).Be described in more detail below these examples and embodiment.

At this, provide an example that relates to the white matter fiber tract imaging tracking based on navigation brain stimulation result of the present invention.

The integration of dissection and functional study for example allows the cerebroma that is in close proximity to brain domain to being in to carry out safer excision.Multi-mode software solution (for example iPlan Cranial software, Brainlab AG, Feldkirchen, Germany) is allowed for the integration of dissection in the preoperative and art of unified plan of neurosurgery and performance data with associated.The clinical value of this planning software depends on inputted patient data's accuracy and reliability.

Diffusion tensor imaging (DTI) and white matter fiber tract imaging tracking are the acceptable MR imaging techniques that utilizes the concept of the anisotropy water diffusion in myelinated nerve fiber.Fibre bundle imaging tracking can realize the three-dimensional reconstruction of white matter bundle and visual, and the information about the relation of these bundles and brain domain and any pathological changes is provided.

For a significant challenge of reconstruct white matter fiber, be for starting the definition of significant seed region in the function of tracing process.In suffering from the patient of cerebroma, patient's functional nerve anatomical structure is subject to the appreciable impact of pathological changes, and this makes to be difficult to only based on anatomic landmark, define seed region pathological changes.

Navigation brain stimulation (NBS) is also referred to as navigation transcranial magnetic stimulation (TMS), and its some parts that can be used for brain is as the mapping of the non-intrusion type accurately of motor cortex.The functional mapping (enum) data of NBS can be directly inputted to operation or treat in planning software, for example iPlan software solution.In addition, NBS data can be used for assisted Selection for the initial seed region of white matter fiber tract imaging tracking.

NBS is a kind of non-intrusion type technology for cerebral cortex electricity irritation.As produce substituting of electric field from be placed on the electrode exposed cortex, in direct cerebral cortex electricity irritation (DCS) in art, navigation transcranial magnetic stimulation (TMS) coil that utilizes NBS to be placed on outside head by triggering to introduce electric field (E field) at intracranial.

When determining motor function, can use the synchro measure of the Motion Evoked Potential (EMG) by electromyography (MEP) to differentiate and verify that the motion in cortex represents region, as DCS.By using special-purpose figure-eight coil and electric field intensity being adjusted into each patient's movement threshold, can realize the excellent resolution that motion represents region.

Equally, can determine and shine upon other functions by suitable method.For example, when definite language and/or cognitive function, can be by job invocation to main body, and before navigation TMS stimulates, between and/or measure/determine afterwards the response of main body to this task.The example shining upon through the cognition of NBS can find in the PCT/FI2012/050218 of submission on March 5th, 2012 and the U.S. Provisional Application 61/448,676 of submission on March 3rd, 2011, and these two applications are incorporated herein by reference at this.

Than DCS, the advantage that NBS mapping has is that it is non-intrusion type, therefore can be used as the planning of operation property and browse patient for performing the operation and the aid of the selection of other therapeutic scheme and using in the preoperative.

Use mapping and the surgical navigation pattern of NBS completely compatible, this is because identical MRI data set can be used as anatomic image, as instructing the two basis in preoperative planning and art.In NBS mapping, MRI data set can be used to the position of the electric field of TMS generation to be linked to each patient's cerebral cortex anatomical structure.The stereotaxis airmanship that use is known, the bootable electric field location of mobile TMS coil is passed through Intracranial structure.MRI data set can be played up by NBS system three-dimensional, and it can be with respect to the orientation of intracranial anatomical structure and position, to be useful feature concerning cerebral cortex somatosensory cortex location.

The DICOM output of motion response mapping can be exported from NBS system, its allow for example in iPlan software, NBS mapping (enum) data and other is mode integrated together with.

Utilize NBS system to carry out the functional mapping of motor cortex.The data file of mapping session is planned to stand by NBS and is retrieved from NBS system, for post processing.By the Motion mapping image generating from corresponding MEP response with DICOM formatted output to before in portable storage device, select and verify maximum field position.

Fig. 1 has shown as being shown in the example that is recorded in the excitation electrical field position in mapping session in NBS system.The position of the intracortical maximum field of NBS computed in software, and according to its corresponding peak-peak MEP amplitude, it is carried out to color coding, thus make thermal map.In thermal map, by white, to causing the position of maximum MEP, carry out color coding.The zoomed-in view that has shown tumor region around on the right of figure, it comprises the position of the maximum field being color-coded.

From mapping session, can generate the DICOM output that is apparent in the stimulation sites NBS screen.In this example, the MEP peak response that is abductor pollicis brevis (APB) for maximum hand muscle is defined as " focus ", and it is used as the seed region of the fibre bundle imaging tracking of tractus pyramidalis in planning software.In this example, APB focus is in close proximity to tumor, as the demonstration that highlights in Fig. 2.

Then patient's MRI data set, NBS map image and DT imaging data are uploaded to iPlan planning software.After image co-registration, from the MEP mapping of NBS Motion mapping session, be presented in three-dimensional navigation image, as shown in Figure 3.Position shown in motor activity can be used as seed region, demonstrates the white matter bundle of primary motor cortex to apply fibre bundle imaging tracking algorithm.Position for the maximum MEP response of the APB muscle for seed region is color coded as green.

Fig. 4 has shown the image of the fiber that is derived from APB focus after the result of fibre bundle imaging tracking not being done to any post processing be converted to 3D object.For example can output to after this 3D object in Brainlab navigation system.In addition, planning can occur in real time in NBS system.In the drawings, tumor marker is red, and APB focus is shown as yellow spheroid.

In function, significant seed region can be determined reliably from non-intrusion type NBS Motion mapping data, and allows white matter fiber construction process more specifically.

This research shows, accurate and reliable non-intrusion type Motion mapping data can greatly promote fibre bundle imaging tracking.The DICOM output of NBS Motion mapping data can be sent in planning system, to select seed region.In addition, planning software can be integrated in NBS system, take based on selected seed and generates the real-time demonstration of white matter fiber as operator.By allowing for example quick, accurate, meaningful and reliable seed to select, these methods can be removed a key obstacle of the extensive clinical practice of DT imaging and fibre bundle imaging tracking.

The fibre bundle imaging tracking of NBS guiding can be used as multimode technology and realizes, for white matter network relevant in preoperative generation function and verify the fiber of institute's reconstruct, as described in the above example.In addition, NBS can be by functional additive technique to existing and new for planning the planning system of surgery track, it can help for example during tumor resection, retaining motor path under crucial cortex, and cortical motor areas.

According to certain embodiments of the present invention, wish mobilizing function, activation volume and/or activation area to be associated with fiber tracking algorithm.

According to the method for this embodiment, can comprise following some or all of step: the stereotaxis of initiating one or more instruments is followed the tracks of, diffusion-weighted MR data for the preparation of fiber tracking, diffusion data is mated with three-dimensional locating frame, in solid space, identify mobilizing function (AF), activation area (AA) or activation volume (AV), with AF, AA or AV, determine target area (A or B), and show resulting fiber.

Diffusion-weighted MR data for the preparation of fiber tracking can comprise for example images match, eddy current correction, Diffusion Tensor Estimation or their combination.For diffusion data is matched to three-dimensional locating frame, system can be used the registration of dissecting MRI and diffusion MR I.Images match and registration can be by from a plurality of images and/or data centralization identification anatomic landmarks and aim at similar/identical sign and complete.In addition,, in order to identify in real time AF, AA or AV, system can comprise the physical modeling of stimulating apparatus.

The method providing at this is for combining stimulation navigation and performance data.These methods can enough intrusive mood brain stimulations or preferably with non-intrusion type, through cranium, are stimulated to realize.Such method comprises following some or all of step: obtain one or more anatomic images of brain, obtain the performance data of brain, and anatomic image is combined with performance data.The example of anatomic image has MRI image and CT image.The example of performance data has positron emission computerized tomography (PET) data, functional mri (fMRI) data and diffusion tensor imaging (DTI) data.

For the performance data of brain and anatomic image are combined, hope can be identified the common sign between anatomic image and performance data.Anatomic image and performance data can be by making the part being at least associated with the part of paying close attention to of brain in performance data combine with the correspondence position registration in anatomic image under the help at common sign.In addition, the assembled view of brain can utilize transcranial magnetic stimulation (TMS) navigation software to carry out Tridimensional positioning alignment.

Anatomic image, performance data and the combination of TMS data and/or the order of registration can be different.In addition, may wish the mutual combination of all data, or only have some data to combine with the data of other types or registration just enough.For example, the three-dimensional locating frame registration that anatomic image, performance data and TMS data can be only utilized with TMS navigation software.Therefore, independent performance data is not directly combined with anatomic image, but data are by three-dimensional locating frame combination indirectly.

In addition, wish to show the assembled view of the brain of the performance data of at least paying close attention to part with the brain being associated for the relevant position with in anatomic image and TMS data.Also can the anatomic image of brain and the head stereoscopic locate mode of main body be alignd with TMS navigation software.

When operation brain stimulation device, importantly should understand and control the network effects that are associated with the region that is stimulated targeting.Combined information can be operator the real-time view that is stimulated the brain network affecting is potentially provided.Therefore, by quilt, stimulate potentially the more complete and real view of the brain network of impact, operator can based on this assembled view select better in brain by the position of TMS pulse targeting.

As mentioned above, in this assembled view or interior position can be marked as definite brain function from navigation TMS.This position can be point or the region on brain surface, or it can be on brain or interior three-D volumes.For example, by stimulating a plurality of specified points (arranging by grid or other) in interest region, and with required response or function, come these regions of labelling, the part that just can shine upon brain with navigation TMS based on this assembled view.In addition, at least some mappings of specific region, can complete on as anatomic image, standard head model etc. at conventional view, and data can be added or be incorporated in anatomic image when creating assembled view.Want mapped region to determine based on this performance data.

As mentioned above, the merging of performance data and anatomic image allows good seed to select.Therefore, hope can be selected the seed region in navigation TMS mapping area from assembled view, so that application fibre bundle imaging tracking algorithm.Fibre bundle imaging tracking algorithm can be used for determining white matter bundle.Then white matter bundle can add in assembled view, as shown in Figure 4.

The advantage of some embodiment of the present invention is, the real-time calculating of fibre bundle imaging tracking algorithm is provided and between stimulation period for navigation TMS operator shows result.Yet this method also can be for off-line mode application fibre bundle imaging tracking algorithm.Such embodiment for example can be used for surgical operation or treatment planning.

As mentioned above, by using seed position and fibre bundle imaging tracking algorithm, can determine the white matter bundle that extends to far-end, end or end from described seed position.This end can comprise dark target and/or target far away, as shown in Figure 7.

Fig. 7 shows a kind of expression of this concept.Adopt the initial position of TMS coil 710 on patient's brain 720 or in brain 720 to produce electric field focus 730.Can for operator, on head model, to the position of electric field focus 730, play up according to physical modeling.This figure schematically shows white matter fiber 740 and how the position of electric field focus (brain surface place or its near) is connected to IC dark target 750.Similarly, white matter fiber 770 is connected to the position of electric field focus the remote object of another position, often near brain surface place or its.DTI and fiber track module can produce that white matter is connected and the playing up of target location, to be shown to operator.

As shown in Figure 8, remote object even can be in the hemisphere contrary with seed.As schematically illustrated in the figure, TMS coil 840 stimulation sites 850, it is for example near the surface of the brain on left hemisphere 820 810 or its.Physical modeling can be played up the position of electric field focus 850.In the present embodiment, can to make the stimulation in region around, these regions be difficult, insecure or undesirable in the existence of tumor or pathological changes 880.Therefore,, by DTI and fiber tracking, can locate the callus white matter fiber that the remote location in a hemisphere 820 is connected with another hemisphere 830.Like this, can be by indirectly stimulating the clog-free position 850 in hemisphere 820 indirectly to stimulate the target area 860 in hemisphere 830.

For verifying that seed is that a kind of method of desirable seed is the corresponding region of the end with by the determined white matter bundle of fibre bundle imaging tracking algorithm that stimulates brain.If the stimulation of end produces desired response, can verify seed, long-range/depths target and the white matter bundle/fiber that connects them.Equally, if the stimulation of end does not produce desired response, existing seed, determined white matter bundle/fiber and/or target is not right probability.In this case, may wish to stimulate end several times with different stimulus parameters.As additional or alternative, for determining that the some or all of method step of end can be used different seeds and/or fibre bundle imaging tracking algorithm/fibre bundle imaging tracking algorithm parameter to repeat.

At this, also proposed to be used to desired locations indirect type in main body brain the method for stimulation is provided, this is by stimulating the diverse location being connected with above-mentioned position intracranial to realize.This method can comprise navigating with by stimulating of some or all and the method step listed above that performance data combines.In addition can comprise some or all of following steps, with by the said method that stimulates navigation and performance data to combine.This method comprises step: the first area of paying close attention in identification brain, and described first area is associated with a specific function conventionally; Determine that the intracranial in brain is connected to the second area of paying close attention to of described first area, the second area breath that wherein identification is paid close attention to is the part based on assembled view, navigation TMS mapping (enum) data or said method at least; And by the second area of paying close attention to in brain, apply to stimulate and indirectly stimulate the first area of paying close attention in brain.For the object of method of the present invention, first area and second area should separate, and connect by white matter bundle, as mentioned above.

According to this method, the method can be used for and/or comprises and apply directly and/or indirectly stimulate.For example, the stimulation applying can be at least one the TMS pulse from TMS coil, a plurality of TMS pulse, or deep brain stimulation, for example DBS probe.

Particularly, for being used in the operation or the method in treatment planning that utilizes DBS probe, the method may further include the step of definite mobilizing function (it is similar to one or more white matter bundle ends activation volume around).On this basis, can determine based on mobilizing function the stimulus parameter of at least one deep brain stimulation probe.

Said method can be used for determining and showing the white matter before or after stimulating.For example, navigation TMS can be used for shining upon the region of brain, to determine that the meeting in brain brings out the ad-hoc location for the desired or maximum response stimulating.Once by this mapping, determined and will be used as the position of seed, just can be in fibre bundle imaging tracking algorithm this specific seed of choice and operation.This method can be guaranteed for determining the in fact responsible specific function of seed of white matter bundle.Yet this method also can be for predicated response and white matter bundle, to provide about the basic dissection of main body brain and emicly visually understand for the operator of navigation brain stimulation system.

Therefore, the method for the prediction intracranial connection of show navigator brain stimulation has been described here.This method can comprise and will stimulate navigation to combine with performance data and carry out indirect type and stimulate the method step listed above of relevant some or all of the desired locations of main body brain with diverse location for being connected with desired locations intracranial by stimulation.In addition, as above to will stimulate navigation to combine with performance data and carry out indirect type and stimulate the said method that the desired locations of main body brain is relevant can comprise following some or all of step with diverse location for being connected with desired locations intracranial by stimulation.This method comprises step: with respect to body head, carry out track navigation TMS coil, wherein at least one part of the position of body head and orientation and assembled view, for example with anatomic image or assembled view whole registration; Determine the prediction that is applied to the specific location in main body by coil is stimulated; The seed for fibre bundle imaging tracking algorithm is appointed as in the position that described prediction is stimulated; Utilize this prediction seed from fibre bundle imaging tracking algorithm, to determine white matter bundle; And in assembled view and/or in assembled view, show predicted white matter bundle.According to some embodiment, the white matter bundle of predicting calculates in real time, and shows before the stimulation of position.

According to the disposal ability of system and/or the complexity of fibre bundle imaging tracking algorithm of implementing this method, the calculating of prediction white matter bundle can be substantially real-time, or can comprise the delay of certain length.If predicted or in advance in respect of the delay in calculating, so it for operator, at them, to want the position of system prediction white matter bundle to carry out hand labeled be desirable.This can be by known input mechanism, for example, when this coil is realized in desired position.The position of coil and orientation also can be recorded.Once calculate and predicted white matter bundle be shown to operator, if it is acceptable that operator assert this bundle, they can aim at TMS coil again, and at coil during in suitable position and optional orientation, and this system can be notified or automatically stimulate main body.

Similarly, the white matter bundle of predicting can be indicated predicted end, and by coil notice or automatically stimulate main body during in suitable position and optional orientation, thereby allow operator to stimulate the end of predicting, as seed region substitute or additional.By stimulating end and measurement or recording responses, can determine accuracy or the effectiveness/ineffectivity of seed, and without stimulating practically seed position.

According to the system of some embodiment of the present invention, comprise the 3 D positioning equipment that can be used for guiding with respect to brain anatomical structure stimulating apparatus.Can adopt guider that stimulating apparatus is directed to suitable anatomical position, this stimulating apparatus is actuated herein, and introduces electric field in the part in the part in brain or in brain.

Stereotaxis Use of Neuronavigation device can guide TMS coil or another stimulating apparatus, for example cortical stimulation electrode, tDCS electrode or DBS lead-in wire.In addition, image processing module can be set, it is for the treatment of causing the diffusion MR I data of dissecting the mapping connecting.

According to the example of system of the present invention, comprise the combination of following parts: (i) stereotaxis guider (its can be optics, magnetic, etc.); (ii) stimulating apparatus, for the acute or long-term impact of the region generating at irriate (based on TMS, through cranium formula electricity, epidural formula is electricity, optics, ultrasonic); (iii) radiotherapy system, it comprises dosage calculating system alternatively; (iv) real-time physical modeling (as electric Field Calculation device), for carrying out modeling to the performance of stimulating apparatus; (v) the image I O system of reads image data; (vi) image processing system of (for example registration, different data sets superposes) for anatomical data is associated from DTI data; (vii) DTI processing system, described processing system can be processed other the data based on diffusion MR alternatively, for example DSI, Q-spheroid data, Q-spatial data, or can be from as the MEG of quiescent condition fMRI, spontaneous/EEG of stimulating or spontaneous/stimulate or other connection data of functional NIRS; (viii) the associated system as shown in Figure 6 that connects (DTI) or function link information (rs-fMRI) and stereotaxis information of dissecting; (ix) associated dissection connects (DTI) or function link information, as the system of rs-fMRI, MEG or EEG and the stereotaxis information relevant to real-time physical modeling.An example of system unit is shown in Fig. 5.This system can be carried out one of said method.

Fig. 5 shows for carrying out an example of the system 500 of said method.System 500 has DTI module, and it preferably communicates by letter with the electric field modeled components of NBS module two-wayly.Two-way communication 530 comprises the seed of electric field modeling is sent to DTI module, for calculating fiber and tensor, processes.DTI module can send information and request to electric field MBM, for example to verify fiber.

Once DTI module has been verified one or more fibers as calculated and alternatively, it just sends to result the head model of NBS module to show, 520, and wherein head model and electric field MBM communicate, and 580.TMS system and NBS module communicate to control stimulation, 530.The label being for example positioned on TMS coil and patient indicates the position of coil and head to tracking system, is respectively 560 and 550.This tracking system and the NBS module of the position of tracking coil and head communicate with regard to position data, and 570.

Said system and method serve many purposes.A kind of exemplary purposes is the seed that helps to determine fibre bundle imaging tracking algorithm.Concrete seed selection can based on or comprise some in following operation:

From different depth sowing, this is because NBS can stimulate brain at different depths.In addition, select the bundle of optimal number to guarantee that seed is in white matter.

Seed selection based on irritability threshold value for example, when the movement threshold of main body 20 millimeters of depths is 55V/m, is chosen seeds from surpass the area of 60V/m.

Seed selection based on normalization motion response.In the time of can surpassing predetermined value in the relation of normalized EMG (mV)/(V/m), start sowing.

Seed selection based on normalized brain response.Can when normalized EMG response (μ V)/(V/m) surpass predetermined value, start sowing.

Seed selection based on view data characteristic.For example,, when white matter signal intensity (T1 or FA) and electric field threshold value are when overlapping.

Eliminating based between DTI target and NBS response or include the seed selection of (as any Boolean calculation) in.For example, can define and/or select seed under cortex, and mapping is connected to the fiber in the region of response stimulation.

Seed selection based on response and non-response, simultaneous display stems from the fiber of response region and non-response region.

Specifically, system and method for the present invention also can be used for the identification of Motion mapping and corticospinal tract.For example, they can be used for combined information based on from DTI and navigation brain stimulation device and carry out cutting apart of white matter under cortex.They also can be used for the checking of the NBS response based on existing bundle, degree of closeness based on following the tracks of.

Further application comprises according to selecting to stimulate area or grid from the overlay information of NBS response and DTI.By the embodiment of system and method for the present invention, can realize the cross validation of DTI and NBS, the Boolean calculation between fiber and NBS response for example, and select some seed/bundles based on cortical excitability.

Sowing also can, according to the response mapping of center of gravity or accumulative total, consequently can improve the reliability of gained fibre bundle.In addition, can realize the DTI targeting based on NBS, being for example placed in seed, end points or the target that posterior limb of internal capsule (PLIC) locates is the cortex target that available this exciting bank obtains.

More specifically, this method and system can be used on the treatment of Cure of depression, visual cortex mapping, language mapping and apoplexy, only lift several examples herein.When Cure of depression for example, method and system of the present invention can be used for identification in marginal texture (as cingulum) or learn the seed in the region (as anterior cingutate) that result is relevant to neuroimaging.In addition in the structure that, seed layout can be relevant in the identification to BA46/BA9, for example superior longitudinal fasciculus II (SLFII), be identified.In addition, seed is arranged and can also in relevant structure such as the region relevant with symptom, language, sensation etc., be identified.

In order to shine upon for visual cortex, method and system of the present invention can be used for the seed at tractus opticus or chiasmatic cistern place and arranges.For for language mapping, before method and system of the present invention is used in mapping or during the bundle of identification from Broca to Wernicke, for example arcuate fascicle.

When using in curing apoplexy, method and system of the present invention for example can be used for identifying allocinesi stimulated zone, and it is found with targeting to reduce the inhibition from intact hemisphere.In addition, for processing aphasia, can identify offside Language Processing region, for example Broca, Wernicke, ring first cortex represent, for targeting to reduce suppressing across hemisphere of intact hemisphere.

In addition, on computer-readable medium or medium can store one or more groups computer-readable instruction, it is for making one or more processors carry out the step of any said method.Described computer-readable medium can be temporary or nonvolatile.

Although described embodiments of the invention and example by being directed to the language-specific of feature and/or method, yet those of ordinary skill in the art will recognize numerous variations and the modification of feature the combination from embodiment, described embodiment and example, this can not depart from scope of the present invention.On the contrary, these concrete features and method disclose as implementing example of the present invention.

Claims

1. for combining non-intrusion type, through cranium, stimulate a method for navigation and performance data, said method comprising the steps of:

Obtain the anatomic image of brain,

Obtain the performance data of brain,

By at least one part of described performance data with from the relevant position registration of described anatomic image, wherein said part is paid close attention to partly and is associated with institute in brain, and

Utilize transcranial magnetic stimulation (TMS) navigation software to come Tridimensional positioning to aim at the assembled view of brain.

2. method according to claim 1, is characterized in that, also comprises step: show that having of brain is directed to the assembled view that at least brain being associated with relevant position on described anatomic image is paid close attention to performance data partly.

3. method according to claim 1 and 2, is characterized in that, utilizes TMS navigation software to make the anatomic image Tridimensional positioning of brain aim at the head of main body.

4. according to the method described in any one in the claims, it is characterized in that, also comprise step: the position by TMS pulse institute targeting of selecting brain based on described assembled view.

5. according to the method described in any one in the claims, it is characterized in that, also comprise step: use definite brain function from navigation TMS to come the position in assembled view or in described assembled view described in labelling.

6. method according to claim 5, is characterized in that, described position is three-D volumes.

7. according to the method described in any one in the claims, it is characterized in that, also comprise step: the part of also shining upon brain with navigation TMS based on described assembled view.

8. method according to claim 7, is characterized in that, the part to be mapped of brain is determined based on described performance data.

9. according to the method described in any one in the claims, it is characterized in that, also comprise step: integrated navigation TMS mapping (enum) data and described assembled view further.

10. method according to claim 9, is characterized in that, also comprises step: in navigation TMS mapping area, select seed region so that application fibre bundle imaging tracking algorithm.

11. methods according to claim 10, is characterized in that, also comprise step: in fibre bundle imaging tracking algorithm, with described seed region, determine white matter bundle.

12. methods according to claim 11, is characterized in that, also comprise step: combine described white matter bundle and described assembled view.

13. according to the method described in claim 11 or 12, it is characterized in that, also comprises step: show the white matter bundle in described assembled view or in described assembled view.

14. according to the method described in any one in claim 10 to 13, it is characterized in that, applies in real time fibre bundle imaging tracking algorithm, and result is shown to the operator of navigation TMS between stimulation period.

15. according to the method described in any one in claim 10 to 13, it is characterized in that, and off-line application fibre bundle imaging tracking algorithm, and result is planned for operation and treatment.

16. according to the method described in any one in claim 10 to 15, it is characterized in that, also comprises the corresponding region of the end with by the definite white matter bundle of fibre bundle imaging tracking algorithm stimulating in brain.

17. methods according to claim 16, is characterized in that, also comprise that the navigation TMS by stub area shines upon to verify that the intracranial between seed region and stub area connects.

18. according to the method described in claim 16 or 17, it is characterized in that, also comprises and determines new seed region, and if described stub area does not correspond to the function of seed region, repeats at least a portion in described method step.

19. according to the method described in any one in the claims, it is characterized in that, also comprises step:

The first area of paying close attention in identification brain, described first area is associated with a specific function,

At least based on described assembled view and/or navigation TMS mapping (enum) data, identify the second area of paying close attention to that intracranial in brain is connected to described first area, and

By the second area of paying close attention to in brain, apply to stimulate and indirectly stimulate the first area of paying close attention in brain.

20. methods according to claim 19, is characterized in that, described second area is different from first area and not overlapping with it.

21. according to the method described in claim 19 or 20, it is characterized in that, the stimulation applying is at least one TMS pulse.

22. according to the method described in claim 19 or 20, it is characterized in that, the stimulation applying is direct stimulation.

23. according to the method described in claim 19,20 or 22, it is characterized in that, the stimulation applying is deep brain stimulation.

24. according to the method described in any one in claim 10 to 23, it is characterized in that, also comprises step: determine mobilizing function, its end that approaches one or more white matter bundles activation volume around.

25. methods according to claim 24, is characterized in that, also comprise step: the stimulus parameter of determining at least one deep brain stimulation probe based on mobilizing function.

26. according to the method described in any one in claim 10 to 25, it is characterized in that, the selection of seed is based on irritability threshold value.

27. methods according to claim 26, is characterized in that, the selection of seed produces the region of the normalization EMG response that surpasses predetermined value when stimulating.

28. methods according to claim 26, is characterized in that, the region when selection of seed produces the normalization EEG response that surpasses predetermined value when stimulating.

29. according to the method described in any one in claim 10 to 28, it is characterized in that, the selection of seed is based on white matter signal intensity and the overlapping region of electric field threshold value.

30. according to the method described in any one in the claims, it is characterized in that, also comprises step:

With respect to body head, carry out track navigation TMS coil, at least one part registration of the position of body head and orientation and described assembled view wherein,

Determine the prediction that is applied to the specific location in main body by coil stimulated,

The seed for fibre bundle imaging tracking algorithm is appointed as in the position that described prediction is stimulated,

Utilize described prediction seed from fibre bundle imaging tracking algorithm, to determine white matter bundle, and

In described assembled view and/or in described assembled view, show predicted white matter bundle.

31. methods according to claim 30, is characterized in that, calculate in real time the white matter bundle of predicting, and before position is stimulated, show the white matter bundle of predicting.

32. according to the method described in claim 30 or 31, it is characterized in that, also comprises step: the stimulation sites that labelling is predicted.

33. according to the method described in any one in claim 30 to 32, it is characterized in that, also comprises step: stimulate and in described assembled view and/or relevant at least one region of the end of the white matter bundle of predicting of interior demonstration.

34. methods according to claim 33, is characterized in that, also comprise step: if the seed of predicting is the germinative seed region for desired zone, carry out labelling.

35. according to the method described in any one in the claims, it is characterized in that, also comprises step: by the Boolean calculation between determined white matter bundle and navigation brain stimulation response, come cross validation performance data and navigation brain stimulation data.

36. according to the method described in any one in claim 19 to 35, it is characterized in that, described first area is Broca, and described second area is Wernicke.

37. according to the method described in any one in the claims, it is characterized in that, described anatomic image is MRI image or CT image.

38. according to the method described in any one in the claims, it is characterized in that, described performance data is positron emission computerized tomography (PET) data, functional mri (fMRI) data or diffusion tensor imaging (DTI) data.

39. 1 kinds for carrying out according to the system of the method described in claim 1 to 36 any one.

40. 1 kinds of computer-readable mediums, have the one group of computer-readable instruction being stored in wherein, and it is for carrying out according to the step in the method described in claim 1 to 36 any one one or more processors.

The computer-readable medium of 41. 1 kinds of nonvolatiles, has the one group of computer-readable instruction being stored in wherein, and it is for carrying out according to the step in the method described in claim 1 to 36 any one one or more processors.

42. 1 kinds of systems for integrated navigation brain stimulation (NBS) and dissection connection mode, described system comprises:

NBS module, and

With diffusion tensor imaging (DTI) module of described NBS module communication,

Wherein, described NBS module structure becomes described DTI module provides seed, and

Described DTI module structure one-tenth offers described NBS module for checking by white matter bundle.

43. according to the system described in claim 42, it is characterized in that, described NBS module comprises real-time physical modeling, stimulating apparatus and stereotactic navigation device.

44. according to the system described in claim 42 or 43, it is characterized in that, described system also comprises the image processing system that is configured to make anatomical data and DTI Registration of Measuring Data.

45. according to the system described in claim 43 or 44, it is characterized in that, described physical modeling System Construction becomes to provide the real-time physical modeling that is produced the electric field that maybe will produce by described stimulating apparatus.

46. according to the system described in any one in claim 42 to 45, it is characterized in that, also comprise display module, it is configured to synchronously show that the part by described NBS module produces the real-time electric field that maybe will produce, and at least one the white matter bundle calculating being calculated by described DTI module.